23 November 2021 - - France-based biotechnology company Transgene (Euronext Paris: TNG) (PAR: TNG) and Japanese IT company NEC Corp. (OTC: NIPNF) have released positive preliminary immunogenicity and clinical data on TG4050, their jointly developed individualized neoantigen cancer vaccine, the companies said.

TG4050 is the first candidate based on Transgene's myvac platform.

Powered by NEC's AI capabilities, it is being evaluated in two ongoing multicenter Phase I trials in patients with ovarian cancer and head and neck cancer.

Prof. Christian H. Ottensmeier, MD, PhD, Professor of Immuno-Oncology, at University of Liverpool and Prof. Jean-Pierre Delord, MD, PhD, general manager of IUCT Oncopole of Toulouse, will share their insights on these early results in two upcoming webcasts, respectively in English and in French (see details at the end of the release).

This individualized immunotherapy is based on Transgene's advanced virus engineering platform myvac and NEC's deep expertise in artificial intelligence.

TG4050 is based on an MVA viral vector which is designed to educate the immune system against each patient's most relevant tumor targets (up to 30 patient-specific neoantigens).

These mutations are identified by next generation sequencing and selected using NEC's proprietary AI-based immunogenicity prediction system. The main goal of the vaccine is to elicit a strong and long-lasting immune response against tumor antigens by targeting class I and class II epitopes.

These two types of responses have been established as key factors in driving a sustained anti-tumor response.

The two studies are designed to assess biological and clinical activity of TG4050 given alone. In particular, the studies were designed to provide insights on the capacity of the selected target neoantigens to induce immune responses against these epitopes and, ultimately, to correlate clinical outcome with biological responses in two indications with significantly different genomic profiles.

The two Phase I clinical trials are exploring the activity of repeated injections of TG4050 as monotherapy in patients with minimal residual disease:

In the ovarian cancer trial, patients receive the vaccine at first signs of asymptomatic relapse of their high grade, advanced-stage disease (after surgery and first-line chemotherapy).

Asymptomatic relapse is defined as the detection of elevated CA-125 (tumor marker of ovarian cancer frequently associated with a relapse) or as low volume radiological disease. The first patient was dosed in August 2020. 

Data have been generated from four patients treated in this trial.

Patients with HPV-negative, advanced-stage head and neck cancer are at high risk of relapse after surgery and adjuvant therapy. In the trial, they are randomized after completion of this primary treatment to receive vaccination (early treatment arm) or to receive TG4050 at relapse (delayed vaccination arm). In this trial, the first patient was dosed in January 2021.

Six patients were randomized in this trial, two in the early treatment arm and four in the delayed vaccination arm.

Overall the data AY were obtained from the first six patients who received TG4050 across the two trials. The primary endpoints of these trials include safety and feasibility. Secondary endpoints include biological activity of the therapeutic vaccine TG4050.

T-cell responses for each targeted mutation were assessed after nine weeks of treatment with TG4050 and compared to baseline for the 4 patients for which evaluable samples were available.

Neoepitope immunoreactive T-cells were quantified by ex vivo IFNgamma ELISPOT.

All four patients developed a robust T-cell response against multiple targeted mutations (neoantigens) with a median of 10 positive responses per patient, confirming the capability of the AI to accurately select immunogenic neoantigens across the two selected indications.

T-cell responses were observed for class I and class II epitopes. They consisted of de novo responses in 64% of observed responses (onset of responses that were absent at baseline) and amplifications of preexisting responses for 36% of vaccine responses.

Additionally, the development of these adaptive responses was concomitant with maturation and activation of the patients' circulating immune cells, suggesting that the vaccine is able to effectively prime the immune system.

Compared to previously reported neoantigen studies, these data reinforce the rationale for TG4050's prediction system and support the validation of the MVA vector as an efficient platform for anti-tumor vaccination.

All immune assessments were conducted by the clinical immunology laboratory of Institut Curie (Paris).

In the ovarian cancer trial, one patient treated after an elevation of CA-125 experienced a normalization of CA-125 without clinical progression during nine months until death from an unrelated chronic illness. Another patient with radiological lesions is stable and is still under treatment with TG4050 nine months after the first injection.

In the head and neck trial early treatment arm (n=2), the two patients have been treated with TG4050 for 10 and five months respectively and are stable. Their treatment is ongoing.

To date, the vaccine has been well tolerated and no related Serious Adverse Events have been reported across the two studies. Adverse events are consistent with previous observations made with the MVA viral vector. They mainly consist of mild and transient symptoms, mostly injection site reactions.

Additional data will be generated in the coming months. Transgene expects to present them at a major oncology conference in 2022.

In both clinical studies, enrollment and patient dosing are progressing in line with our expectations. Overall, Transgene plans to treat 13 patients in the ovarian cancer trial and 30 patients in the head and neck trial.

TG4050 is being evaluated in two Phase I clinical trials for patients with ovarian cancer (NCT03839524) and HPV-negative head and neck cancers (NCT04183166).

In a first Phase I trial, TG4050 is being administered to patients with HPV-negative head and neck cancer. A personalized treatment is created for each patient after they complete surgery and while they receive an adjuvant therapy.

Half of the participants receive their vaccine immediately after they complete their adjuvant treatment. The other half is given TG4050 as an additional treatment at the time of recurrence of the disease. This randomized study is evaluating the treatment benefits of TG4050 in patients who have a high risk of relapse.

Up to 30 patients will receive TG4050 in France, in the UK and in the USA.

The principal investigator of the trial is Prof. Christian Ottensmeier, MD, PhD, Consultant Medical Oncologist at the Clatterbridge Cancer Centre and Professor of Immuno-Oncology at the University of Liverpool.

In France, the clinical trial is being conducted, at Institut Curie, Paris, by Prof. Christophe Le Tourneau, MD, PhD, Head of the Department of Drug Development and Innovation and at the IUCT-Oncopole, Toulouse, by Prof. Jean-Pierre Delord.

In the USA, the trial is being led by Dr. Yujie Zhao, MD, PhD, at the Mayo Clinic. Endpoints of the trial include safety, feasibility and biological activity of the therapeutic vaccine.

In parallel, a Phase I clinical trial of TG4050 is enrolling patients with ovarian cancer. The first patient has been dosed in the USA.

myvac is a viral vector (MVA Modified Vaccinia Ankara) based, individualized immunotherapy platform that has been developed by Transgene to target solid tumors. myvac-derived products are designed to stimulate the patient's immune system, recognize and destroy tumors using the patient's own cancer specific genetic mutations.

Transgene has set up an innovative network that combines bioengineering, digital transformation, established vectorization know-how and unique manufacturing capabilities.

Transgene has been awarded "Investment for the Future" funding from Bpifrance for the development of its platform myvac. TG4050 is the first myvac-derived product being evaluated in clinical trials.

TG4050 is an individualized immunotherapy being developed for solid tumors that is based on Transgene's myvac technology and powered by NEC's longstanding artificial intelligence expertise.

This virus-based therapeutic vaccine encodes neoantigens (patient-specific mutations) identified and selected by NEC's Neoantigen Prediction System.

The prediction system is based on more than two decades of expertise in AI and has been trained on proprietary data allowing it to accurately prioritize and select the most immunogenic sequences.

TG4050 is designed to stimulate the immune system of patients in order to induce a T-cell response that is able to recognize and destroy tumor cells based on their own neoantigens. This individualized immunotherapy is developed and produced for each patient.